Molecular Biology as a Computational Science

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Lecture 5:

Proteins

Joseph L. Hellerstein

jlheller@uw.edu

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Agenda



_{Importance of proteins}



_{Proteins and peptide bonds}



_{Protein structures}



_{Amino acids}



_{Forces between amino acids}



_{Example of protein function -}

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Importance of Proteins

(4)

Central Dogma & Proteins

Protein

(5)

Amino Acids

Side chains (R)

Amine terminus

Carboxyl terminus

Alpha Carbon

(6)

Chemical UML

• _{A type has}

• _Other

types

• _Bonds

• _{Bond roles}

(7)

Amino Acids (AAs) in UML

(8)

Peptides and Proteins



_{A peptide is a short chain of amino}

acids



_{A protein is a long peptide}



_{Peptide/protein type structure}



Amino acids

(9)

Peptide

c

v

c

v

_v

c

_v

AminoResidue

Amine terminator

Carboxyl terminator

9 Molecular Biology as a Computational Science. Joseph L. Hellerstein, 2014.

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Unterminated Peptide

Unterminated peptide chain of length 4

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Peptide

c

v

c

v

_v

c

_v

Unterminated Peptide

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Protein

Structure



_{Primary structure}



_{Linear sequence of AAs}



_{Secondary structure}



_{Interactions within 10 AA}



_{Tertiary structure}



_{Interactions within the same peptide}



_{Quarternary structure}



Interactions between peptide chains

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Primary Structure:

Linear Sequence

Molecular Biology as a Computational Science. Joseph L. Hellerstein, 2014. 13

Start

Stop

Amino Acid

Nucleobase

Hypothesis: Primary structure determines

secondary, tertiary, and quaternary

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Secondary Structure:

alpha-helix

Short range interactions

Hydrogen bonds form because of interactions between

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Secondary Structure: Beta

sheets

15 Molecular Biology as a Computational Science. Joseph L. Hellerstein, 2014.

Hydrogen bonds between backbone

substituents. Here, the interactions are

between parallel chains.

(Wikipedia)

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Tertiary Structure

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Quarternary Structure

Alpha

Beta

Alpha

Beta

Heme (O carrying)

(18)

Relating Tertiary to Primary

Structure

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Relating Tertiary to Primary

Structure

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Beliefs about Proteins



_{A protein’s structure uniquely}

determines its function



_{A protein’s primary structure}

determines all other

structures



_{Implies that higher order}

structure is completely

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Remember These

Types

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Hydrophobic AAs

Alanine, Ala, AIsoleucine, Ile, ILeucine, Leu, LValine, Val, V

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Polar Neutral AAs

Asparagine, Asn, N Cystenine, Cys, C

Glutamine, Gln, Q

Methionine, Met, M

Serine, Ser, S

Threonine, Thr, T

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Charged AAs

Aspartic acid, Asp, D

Glutamic acid, Glu, E

+

(25)

Other

Glycine, Gly, G

Proline, Pro, P

(26)

(27)

But Why Do Proteins

Fold?

For tertiary and quaternary structure,

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Bonds Between AA Side

Chains

Dissulfide bonds

Hydrogen bonds

(H with O or N)

Hydrophobic

“bonds”

polar

Non-polar

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Protein Questions



_{Between which AA will there be hydrophobic}

bonds?



_{Ionic bonds?}



_{Which AA is good for tight turns?}



_{Which will disrupt the folding pattern?}



_{Between which AAs will there be H bonds?}

Bonds

1.Disulfide

2.Hydrogen

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Answers



_{Between which AA will there be}

hydrophobic interactions?



Hydrophobic side chains



_{Ionic bonds?}



Positive and negatively charged



_{Which AA is good for tight turns?}



Gly(cine) since it has the smallest side chain (H)



_{Which will disrupt the folding pattern?}



Pro(line) since it’s very stiff



_{Between which AAs will there be H bonds?}

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What Bonds Between Side Chains?

(Wikipedia)

Bonds

1.Disulfide

2.Hydrogen

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Amino Acids and Forces

Molecular Biology as a Computational Science. Joseph L. Hellerstein, 2014. 3 2

Hydro

-phobi

c

Polar Charg

ed

Neg

Charg

ed

Pos

Hydro

-phobi

c

Hydrophob

ic

Interaction

s

Polar

Dissulfide

Bonds,

Hydrogen

Bonds

Hydrogen

Bonds

Hydrogen

Bonds

Charg

ed

Neg

Hydrogen

Bonds?

Ionic Bonds,

Hydrogen

Bonds

Charg

ed

(33)

A Protein Example: Hemoglobin



Hemoglobin provides oxygen

transport in mammals



97% of the red blood cells' dry content

(by weight)



Increases blood oxygen capacity by 70X

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Hemoglobin Use Cases

Core concept: Animals have

rapidly varying needs for

oxygen that require:



_{Bind oxygen where it’s}

plentiful



_{Release oxygen where it’s}

needed (e.g., muscles)

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Hemoglobin Oxygen

Binding



_{All 4 subunits can bind oxygen (in their}

heme groups)



_{Binding oxygen causes a hemoglobin}

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Hemoglobin Dynamics

Oxygen Release



Low pH, high CO

₂



_{Indicators of greater}

oxygen needs



_{Increases rate of}

release of oxygen

0

1 ₁

2 ₂

3 ₃

4 ₄

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Review: Explain the

Following

Name the bonds

between side

chains.

Describe the

structure of this

protein.